Neuronal loss in man, whether by disease, aging or accident is permanent. Central nervous system (CNS) neurons do not regenerate. However, recent studies using the rat as a model have demonstrated that transplanted neurons can reinnervate injured areas of the brain under some conditions. By better understanding that factors involved in the successful transplantation of CNS neurons, we may be able to alleviate some of the problems that occur in neural deficiencies. We intend to define the important variables involved in transplanting hypothalamic neurons, identifying those which are necessary for the structural and functional integration of transplanted tissue. We will then begin preliminary studies to determine how neural grafts may be used in repairing CNS lesions. A major feature of our proposal involves taking vasopressin (AVP) synthesizing neurons from normal donors, and grafting them into hosts who genetically lack those neurons (Brattleboro strain, DI rats). Because the host's brain lacks AVP, the transplanted neurons and their axonal processes can be unequivocally identified by immunohistochemical straining for vasopressin. We will examine the architecture of the grafted tissue, its integration with host tissue and its ultrastructural features by light and electron microscopy. Functional development of the graft will be judged in terms of vasopressin synthesis and release into the systemic circulation. These criteria are to be determined, respectively, by the presence of immunoreactive AVP in graft homogenates and the host's ability to conserve water. (Due to lack of vasopressin, DI rates drink about twn times as much water daily as normal animals. AVP from the graft will decrease water consumption).